Glucokinase and glucokinase activator

Abstract

Glucokinase (GK) plays a pivotal role in glucose homeostasis as the glucose sensor in the pancreas and liver. Loss of function of GK results in hyperglycemia, and gain of function causes congenital hyperinsulinemic hypoglycemia. We speculate that the progressive loss of GK at both mRNA and protein levels in the islets and liver would be the key mechanism for type 2 diabetes pathogenesis. The development of GK activator (GKA) as an anti-diabetic drug has been endeavored for several decades. The failure of the early development of GKAs is due to the limitation of understanding the mode of GKA action. The success of dorzagliatin in the treatment of type 2 diabetes has brought new hope for GK in setting a good model for repairing the underlying defects in the pancreatic islets and liver of T2D patients.